IL-6反义寡核苷酸对骨吸收的抑制作用

Inhibition on the bone resorption by IL-6 antisense oligonucleotides in vitro

目的 :探讨IL -6反义寡核苷酸在体外对骨吸收的抑制作用及意义。方法 :分离培养新生小鼠颅盖骨 ,并分别用IL -6硫代反义寡核苷酸 (ASON )、无义寡核苷酸 (NSO )、IL -6或ASON与IL -6联合作用颅盖骨 ,未加药组为对照。培养一定时间后 ,测定培养上清液的钙含量 ,将实验组钙含量与对照组钙含量比值作骨吸收指数。结果 :ASON( 5.0m/L)分别作用 12、2 4、48h后 ,颅盖骨骨吸收指数呈时间依赖性降低。作用 48h后 ,ASON使颅盖骨骨吸收指数呈剂量依赖性降低 ;IL -6则使其呈剂量依赖性升高 ;ASON可轻度降低IL -6升高的骨吸收指数 ;ASON( 5μm /L)对有或无IL -6培养的颅盖骨骨吸收抑制率分别为 10 .8%、19.3 % ;NSO对骨吸收指数无影响。结论 :IL

Obiective To investigate the Inhibi ti on on the bone resorption by IL-6 antisense oligonucleotides in vitro. Methods Calvaria of newborn mice was cultured and exposed to IL-6 p hosphorolated antisense oligonucleotides(ASON), nosense oligonucleotide(NSO), IL-6, at various dosages respectively,ASON+IL-6, or without the above agents(con trol).The calcium concentration in culture medium was detamined by atomic absorp tion spectrum apparatus.The calcium concentration of treated groups versus that of the control was used as the absorption index. Results When the bone was treated by ASON(5 μm/L) for 12,24 or 48 hours, the absorption index.was decreased in time-dependent manner.48 hours after treatment, the abso rption index was decreased in dose-dependent manner when the bone was exposed to ASON and those were increased in dose-dependent manner when the bone was expose d to IL-6. The absorption index elevated by IL-6(40 ng/mL) was only slightly res tricted by ASON(5 μm/L); the inhibit rate of bone resorpotion by ASON was 10.8% and 19.3% respectively when the bone cultured with or without IL-6.The absorpti on index was not varied by NSO. Conclusion IL-6 antisense oligonucleotides can reduce bone resorption of calvariain vitro.